Background: Increasing evidence implies the participation of long non-coding RNAs (lncRNAs) in chemoresistance to cancer treatment. Their role and molecular mechanisms in breast cancer chemoresistance, nevertheless, are yet not considerably elucidated. In this work, we research the function of small nucleolar RNA host gene 15 (SNHG15) in cisplatin (DDP) resistance of breast cancer and uncover the underlying molecular mechanism. Methods: SNHG15 and miR-381 expression levels were detected using Quantitative realtime PCR (qRT-PCR) analysis. The functional roles of SNHG15 and miR-381 in breast cancer were determined using MTT assay and flow cytometry analysis. The effect of SNHG15 on miR-381 expression was determined using Luciferase reporter assay, RNA immunoprecipitation (RIP) assay and qRT-PCR analysis. Results: SNHG15 was found to be up-regulated in cisplatin resistant breast cancer tissues and cell lines. Breast cancer patients with high SNHG15 expression had a poor prognosis. SNHG15 silencing enhanced cisplatin sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. Additionally, SNHG15 could function as a miR-381 sponge. miR-381 overexpression could overcome cisplatin resistance. miR-381 knockdown countered SNHG15 knockdown-mediated enhancement of cisplatin sensitivity in MCF-7/DDP and MDA-MB-231/DDP cells. Besides, SNHG15 knockdown facilitated cisplatin sensitivity of cisplatin resistant breast cancer cells in vivo. Conclusion: In summary, SNHG15 knockdown overcame cisplatin resistance of breast cancer by sponging miR-381, providing a novel therapeutic target for breast cancer.
Breast cancer is a one of the most malignant threats among women worldwide. However, the mechanism underlying breast cancer development remains unclear. Long noncoding RNAs (lncRNAs) have been reported to participate in breast cancer. Whether lncRNA LINC01857 is involved in breast cancer requires investigation. In this study, we found that LINC01857 was highly expressed in breast cancer tissues and cells (p < 0.05). High LINC01857 expression predicted poor prognosis in breast cancer patients. Functionally, LINC01857 silencing impaired proliferation and enhanced apoptosis of breast cancer cells (
p < 0.05). Decreased LINC01857 inhibited breast cancer cells migration and invasion ability (
p < 0.05). In terms of mechanism, LINC01857 promoted H3K27Ac deposition on CREB1 promoter and initiated its transcription by recruiting CREBBP. Overexpression of CREB1 reversed the biological behavior of breast cancer cells induced by LINC01857 silencing (
p < 0.05). Taken together, our findings demonstrated that LINC01857 promoted breast cancer development by promoting H3K27Ac and CREB1 transcription via enhancing CREBBP enrichment in the CREB1 promoter region.
Breast cancer remains a general-threat event in the health of women. Currently, increasing records indicate that long non-coding RNA maternally expressed 3 (MEG3) plays a central role in breast cancer. The current research focused on the function of MEG3 in paclitaxel (PTX)-resistance and human breast cancer growth. Levels of MEG3, microRNA (miR)-4513, and phenazine biosynthesis-like domaincontaining protein (PBLD) were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assays. 3-(4.5-dimethylghiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) assay was performed to examine the IC 50 of PTX and cell proliferation in breast cancer cells. In addition, cell apoptosis was determined utilizing flow cytometry. Transwell was conducted to assay cell migration and invasion in MCF-7 and MDA-MB-231 cells. The interaction between miR-4513 and MEG3 or PBLD was expounded via dual-luciferase reporter assay. Levels of MEG3 and PBLD were decreased, but miR-4513 level was triggered in breast cancer tissues and cell lines. Overexpression of MEG3 could reinforce cell apoptosis, impede proliferation, migration, invasion, and the IC50 of PTX in breast cancer cells. Moreover, the impact of miR-4513 inhibitor on cell progression and PTX-resistance was overturned by MEG3 deficiency. Interestingly, miR-4513 mimic could abolish the role of PBLD upregulation in cell behaviors and PTX-resistance in MCF-7 and MDA-MB-231 cells. Finally, the expression of PBLD was co-modulated by miR-4513 and MEG3 in vitro. MEG3/miR-4513/PBLD axis modulated PTX-resistance and the development of breast cancer cells, which might provide a promising therapeutic strategy for breast cancer.
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